Obesity, as a global public health concern, causes a series of metabolic disorders and other diseases. Browning of white fat (white adipocytes transforming to beige adipocytes) offers an attractive approach for obesity treatment. In the present study, aptamer-functionalized nanogel of gold nanoclusters (AuNCs), termed Apt-NG, was developed as the targeted delivery vehicle of browning agent docosahexaenoic acid (DHA). Apt-NG has multiple advantages, including nanoscale size, strong autofluorescence, low toxicity, and excellent targeting capability to white adipocytes. After treatment with DHA@Apt-NG, the morphology of lipid droplets changed evidently; meanwhile the triglyceride level decreased while the mitochondrial activity increased. The DHA@Apt-NG treatment effectively up-regulated the mRNA expression levels of Ucp1, Pgc-1α, Pparg, and Prdm16, which play important roles in browning of white adipocytes. This study provides a feasible strategy to achieve efficient browning of white adipocytes based on targeted delivery nanosystems, inspiring a new idea for obesity treatment.